Precise biomarkers for predicting the therapeutic efficacy of molecularly targeted drugs are limited at the protein level; thus, it has been important to broadly scrutinize individual cancer driver gene mutations for effective cancer treatments. Multiplex cancer genome profiling can comprehensively identify gene mutations that are therapeutic targets using next-generation sequencing (NGS). In addition, circulating tumor DNA (ctDNA) is a DNA fragment released into the blood by tumor cell-derived cell death or apoptosis. Liquid biopsy with ctDNA is a novel clinical test for identifying genetic mutations in an entire population noninvasively, in real-time, and heterogeneously. Although there are several reports on ctDNA, fewer have evaluated ctDNA with NGS before an initial treatment for breast cancer patients. Therefore, we examined whether analyzing tumor-associated gene mutations in primary breast cancer based on ctDNA could serve as a biomarker for prognosis and optimal treatment selection. Ninety-five primary breast cancer patients treated at our department from January 2017 to October 2020 were included. Pretreatment plasma samples were subjected to NGS analysis of ctDNA, and correlations with patients’ clinicopathological characteristics were evaluated. Fifty-nine (62.1%) patients were positive for ctDNA. ctDNA tended to be positive in hormone receptor-negative, andTP53(34%),BRCA1(20%), andBRCA2(17%) gene mutations were more frequent. Regarding recurrence-free survival, the prognosis was poor in theTP53and/orBRCA1mutation-positive groups, especially in triple-negative breast cancer (TNBC) patients. In conclusion, the results of this study indicate that ctDNA with liquid biopsy could identify the poor prognosis group before treatment among TNBC patients and for those for whom optimal treatment selection is desirable; additionally, optimal treatment could be selected according to the ctDNA analysis results.
目前，在蛋白质水平上预测分子靶向药物疗效的精准生物标志物仍较为有限，因此广泛筛查个体癌症驱动基因突变对于实现有效的癌症治疗至关重要。多重癌症基因组分析能够利用下一代测序技术全面识别可作为治疗靶点的基因突变。此外，循环肿瘤DNA是肿瘤细胞通过死亡或凋亡释放到血液中的DNA片段。基于ctDNA的液体活检作为一种新型临床检测手段，能够以无创、实时、异质性的方式在全人群中识别基因突变。尽管已有若干关于ctDNA的研究报道，但在乳腺癌患者初始治疗前使用NGS技术评估ctDNA的研究仍相对较少。为此，本研究探讨了基于ctDNA分析原发性乳腺癌相关基因突变是否可作为预后判断及优化治疗方案选择的生物标志物。研究纳入2017年1月至2020年10月期间在我科接受治疗的95例原发性乳腺癌患者，对其治疗前血浆样本进行ctDNA的NGS分析，并评估其与患者临床病理特征的相关性。结果显示，59例（62.1%）患者ctDNA检测呈阳性，其中激素受体阴性患者更易出现ctDNA阳性，且TP53（34%）、BRCA1（20%）和BRCA2（17%）基因突变频率较高。在无复发生存期方面，TP53和/或BRCA1突变阳性组预后较差，特别是在三阴性乳腺癌患者中表现尤为显著。综上所述，本研究结果表明，液体活检联合ctDNA分析能够在治疗前识别三阴性乳腺癌患者中的预后不良群体，并为需要优化治疗方案的患者提供依据；同时，可根据ctDNA分析结果选择最佳治疗方案。
肿瘤(癌症)患者之家